A chemical pharmacological study of the catecholamine neuronal uptake system is proposed in which N-(2-chloroethyl)-N-(2-Methylbenzyl)-ethylamine (2MeBCE) and related compounds are used as chemical probes to examine the role of the catecholamine transport system in the action of compounds such as amphetamine, cocaine and desmethylimipramine. 2MeBCE is an alkylating type irreversible inhibitor of uptake that can be labelled with tritium. This compound and its congeners are presently being studied for specificity and potency as inhibitors of uptake. When optimal conditions for induction of inhibition have been established changes in the actions of readily diffusable drugs that are known to interact with the carrier will be assessed and interpreted in terms of the irreversibly inhibited carrier. Interaction of such drugs with the carrier will also be studied with tritium labelled inhibitor where binding, and protection of binding of the label by drugs will be examined. The exeriments will be conducted in brain and vascular tissue. Experiments will also be conducted with a cell line (PC-12) to evaluate its suitability for studies on the neuronal carrier. Additional studies are planned to develop more specific inhibitors of DA uptake.